circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis.
circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis.
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circ_0003204通过miR-370-3p/HDAC4轴调节人脂肪干细胞的成骨分化
DOI：
10.1038/s41368-022-00184-2
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发表时间：
2022-06-21
影响因子：
14.9
通讯作者：
Liu, Jun
中科院分区：
文献类型：
--
作者：
Yu, Liyuan;Xia, Kai;Zhou, Jing;Hu, Zhiai;Yin, Xing;Zhou, Chenchen;Zou, Shujuan;Liu, Jun
人脂肪来源干细胞（hASCs）是一种很有前途的骨组织再生细胞类型。环状rna （circRNAs）已被证明在调节各种细胞分化和参与间充质干细胞成骨过程中发挥关键作用。然而，circrna在成骨过程中如何调节hASCs尚不清楚。在此，我们发现circ_0003204在hASCs成骨分化过程中显著下调。通过siRNA敲低circ_0003204或慢病毒过表达circ_0003204证实circ_0003204可负向调节hASCs的成骨分化。我们通过双荧光素酶报告实验和救援实验来验证circ_0003204通过海绵miR-370-3p调节成骨分化。我们预测并证实了miR-370-3p在HDAC4 mRNA的3 ' -UTR中具有靶点。随后的修复实验表明circ_0003204通过miR-370-3p/HDAC4轴调控hASCs的成骨分化。随后的体内实验表明，在小鼠骨缺损模型中，沉默circ_0003204增加骨形成，促进成骨相关蛋白的表达，而过表达circ_0003204则抑制骨缺损修复。我们的研究结果表明circ_0003204可能是促进hASCs修复骨缺损的一个有希望的靶点。
Human adipose-derived stem cells (hASCs) are a promising cell type for bone tissue regeneration. Circular RNAs (circRNAs) have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis. However, how circRNAs regulate hASCs in osteogenesis is still unclear. Herein, we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs. Knockdown of circ_0003204 by siRNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs. We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p. We predicted and confirmed that miR-370-3p had targets in the 3′-UTR of HDAC4 mRNA. The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis. Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model, while overexpression of circ_0003204 inhibited bone defect repair. Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.
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